In the past year, our efforts focus on the role of microbe, including gut microbiota, in regulation of host NAD metabolism, the role of SIRT1 in regulation of intestinal tissue homeostasis and animal development, as well as the role of non-acetylation protein acylations in regulation of cancer cell metabolism and stem cell differentiation. The protein deacylation activity of sirtuin family of HDACs is exclusively dependent on NAD+, a molecule essential for life. NAD+ is a cofactor for hundreds of metabolic reactions in all cell types, plays an essential role in diverse cellular processes including metabolism, DNA repair, and aging. However, how NAD metabolism is impacted by the environment remains unclear. Mammalian cells have the capacity to synthesize NAD+ from the amino acid tryptophan (de novo pathway), nicotinic acid (Preiss-Halder pathway), or nicotinamide (salvage pathway), the latter representing the main source of cellular NAD+. In one of our recent studies, we unexpectedly discovered that bacteria, including mycoplasmas and E. coli, interact with human host cells through NAD+ biosynthesis. We found that bacteria confer mammalian cells with the resistance to inhibitors of NAMPT, the rate limiting enzyme in the vertebrate amidated NAD salvage pathway. Mechanistically, a microbial nicotinamidase (PncA) that converts nicotinamide to nicotinic acid, a key precursor in the alternative deamidated NAD salvage pathway, is necessary and sufficient for this protective effect. We further demonstrate that this bacteria-mediated deamidation is necessary for the hepatic NAD-boosting effect of oral nicotinamide and nicotinamide riboside supplementation using stable isotope tracing and microbiota-depleted mice. Collectively, our findings reveal a crucial role of bacteria-enabled deamidated pathway in host NAD metabolism. The discovery of this host-microbe metabolic crosstalk that links two NAD salvage pathways in mammals will open the door for new therapeutic approaches targeting NAD metabolism via manipulation of the microbiome. Currently, a manuscript describing this study is under revision. In the past decade, a panel of novel short-chain and long-chain lysine acylations (or lipid lysine acylations) has been identified in addition to protein acetylation. Compared to histone acetylation, these lipid lysine acylations are mediated by intermediate metabolites from different metabolic pathways, pose distinct genomic distributions, display distinct affinities to various modifiers (e.g. writers, erasers and readers), and have a greater ability to activate gene expression. However, physiological outcomes associated with these new histone acylations remain largely unknown. In a recent study, we assessed the impact of histone crotonylation, one of the first discovered non-acetyl histone lysine acylations, on lineage commitment of pluripotent stem cells and early embryogenesis. Histone crotonylation is derived from crotonyl-CoA, an intermediate metabolite during mitochondrial or peroxisomal fatty acid oxidation as well as lysine and tryptophan metabolism. We show that key crotonyl-CoA producing enzymes mediating fatty acid oxidation are specifically induced in endodermal cells during differentiation of human embryonic stem cells (hESCs) in vitro and in mouse embryos, where they function to increase histone crotonylation and enhance endodermal gene expression. Consistently, chemical or genetic enhancement of histone crotonylation promotes endoderm differentiation of hESCs, whereas deletion or blocking the nuclear translocation of crotonyl-CoA producing enzymes reduces histone crotonylation and impairs endoderm differentiation in vitro and in vivo. Our study uncovers a novel histone crotonylation-mediated mechanism that promotes endodermal commitment of pluripotent stem cells, which may have important implications in new therapeutic strategies against a number of human diseases. Currently, a manuscript describing this study is under review.